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Nitric oxide delivery during cardiopulmonary bypass reduces acute kidney injury: A randomized trial.
Kamenshchikov, NO, Anfinogenova, YJ, Kozlov, BN, Svirko, YS, Pekarskiy, SE, Evtushenko, VV, Lugovsky, VA, Shipulin, VM, Lomivorotov, VV, Podoksenov, YK
The Journal of thoracic and cardiovascular surgery. 2022;(4):1393-1403.e9
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Abstract
OBJECTIVE Acute kidney injury (AKI) is a serious complication of cardiac surgery with cardiopulmonary bypass (CPB). The aim of this study was to evaluate the effects of nitric oxide (NO) supplementation to the CPB circuit on the development of cardiac surgery-associated AKI. METHODS This prospective randomized controlled study included 96 patients with moderate risk of renal complications who underwent elective cardiac surgery with CPB. The study protocol was registered at ClinicalTrials.gov (identifier NCT03527381). Patients were randomly allocated to either NO supplementation to the CPB bypass circuit (NO treatment group; n = 48) or usual care (control group; n = 48). In the NO treatment group, 40-ppm NO was administered during the entire CPB period. The primary outcome was the incidence of AKI. RESULTS NO treatment was associated with a significant decrease in AKI incidence (10 cases [20.8%] vs 20 cases [41.6%] in the control group; relative risk, 0.5; 95% confidence interval, 0.26-0.95; P = .023) and a higher median urine output during CPB (2.6 mL/kg/h [interquartile range (IQR), 2.1-5.08 mL/kg/h] vs 1.7 mL/kg/h [IQR, 0.80-2.50 mL/kg/h]; P = .0002). The median urinary neutrophil gelatinase-associated lipocalin level at 4 hours after surgery was significantly lower in the NO treatment group (1.12 ng/mL [IQR, 0.75-5.8 ng/mL] vs 4.62 ng/mL [IQR, 2.02-34.55 ng/mL]; P = .005). In the NO treatment group, concentrations of NO metabolites were significantly increased at 5 minutes postclamping, at 5 minutes after declamping, and at the end of the operation. Concentrations of proinflammatory and anti-inflammatory mediators and free plasma hemoglobin did not differ significantly between the 2 groups. CONCLUSIONS NO administration in patients at moderate risk of renal complications undergoing elective cardiac surgery with CPB was associated with a lower incidence of AKI.
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Change in Exercise Performance and Markers of Acute Kidney Injury Following Heat Acclimation with Permissive Dehydration.
Haroutounian, A, Amorim, FT, Astorino, TA, Khodiguian, N, Curtiss, KM, Matthews, ARD, Estrada, MJ, Fennel, Z, McKenna, Z, Nava, R, et al
Nutrients. 2021;(3)
Abstract
Implementing permissive dehydration (DEH) during short-term heat acclimation (HA) may accelerate adaptations to the heat. However, HA with DEH may augment risk for acute kidney injury (AKI). This study investigated the effect of HA with permissive DEH on time-trial performance and markers of AKI. Fourteen moderately trained men (age and VO2max = 25 ± 0.5 yr and 51.6 ± 1.8 mL.kg-1.min-1) were randomly assigned to DEH or euhydration (EUH). Time-trial performance and VO2max were assessed in a temperate environment before and after 7 d of HA. Heat acclimation consisted of 90 min of cycling in an environmental chamber (40 °C, 35% RH). Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were assessed pre- and post-exercise on day 1 and day 7 of HA. Following HA, VO2max did not change in either group (p = 0.099); however, time-trial performance significantly improved (3%, p < 0.01) with no difference between groups (p = 0.485). Compared to pre-exercise, NGAL was not significantly different following day 1 and 7 of HA (p = 0.113) with no difference between groups (p = 0.667). There was a significant increase in KIM-1 following day 1 and 7 of HA (p = 0.002) with no difference between groups (p = 0.307). Heat acclimation paired with permissive DEH does not amplify improvements in VO2max or time-trial performance in a temperate environment versus EUH and does not increase markers of AKI.
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Intensity of Renal Replacement Therapy and Duration of Mechanical Ventilation: Secondary Analysis of the Acute Renal Failure Trial Network Study.
Sharma, S, Kelly, YP, Palevsky, PM, Waikar, SS
Chest. 2020;(4):1473-1481
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Abstract
BACKGROUND Randomized clinical trials have failed to show benefit from increasing intensity of renal replacement therapy (RRT) for acute kidney injury, but continue to be frequently used. In addition, intensive RRT is associated with an increase in adverse events potentially secondary to small solute losses, such as phosphate. We hypothesized that, compared with less-intensive RRT, intensive RRT would lead to longer duration of mechanical ventilation. RESEARCH QUESTION Does more-intensive renal replacement therapy in critically ill patients with acute kidney injury increase time to extubation from mechanical ventilation when compared with less-intensive therapy? STUDY DESIGN AND METHODS The Acute Renal Failure Trial Network study was a randomized multicenter trial of more-intensive (hemodialysis or sustained low-efficiency dialysis six times per week or continuous venovenous hemodiafiltration at 35 mL/kg per hour) vs less-intensive (hemodialysis or sustained low-efficiency dialysis three times per week or continuous venovenous hemodiafiltration at 20 mL/kg per hour) RRT in critically ill patients with acute kidney injury. Of 1124 patients, 907 who were supported by mechanical ventilation on study initiation were included in this Cox-proportional hazards analysis. The primary outcome was the time to first successful extubation off mechanical ventilation. RESULTS Patients who were assigned randomly to more-intensive RRT had a 33.3% lower hazard rate of successful extubation (hazard ratio, 0.67; 95% CI, 0.52-0.88; P < .001) when compared with patients who were assigned to less-intensive RRT. Patients who were assigned to more-intensive RRT had, on average, 2.07 ventilator-free days, compared with 3.08 days in those who were assigned to less-intensive RRT (P < .001) over 14 days from start of the study. INTERPRETATION Critically ill mechanically ventilated patients who were assigned randomly to more-intensive RRT had longer duration of mechanical ventilation compared with those who were assigned to less-intensive RRT. The reasons for this, such as excessive phosphate loss from more-intensive RRT, deserve further study to optimize the safety and effectiveness of CRRT delivery. This was a post hoc analysis of the Acute Renal Failure Trial Network study; clinical trial registration of the original trial is NCT00076219.
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Renal effects of norepinephrine-induced variations in mean arterial pressure after liver transplantation: A randomized cross-over trial.
Skytte Larsson, J, Bragadottir, G, Redfors, B, Ricksten, SE
Acta anaesthesiologica Scandinavica. 2018;(9):1229-1236
Abstract
BACKGROUND Acute kidney injury is commonly seen after liver transplantation. The optimal perioperative target mean arterial pressure (MAP) for renal filtration, perfusion and oxygenation in liver recipients is not known. The effects of norepinephrine-induced changes in MAP on renal blood flow (RBF), oxygen delivery (RDO2 ), glomerular filtration rate (GFR) and renal oxygenation (=renal oxygen extraction, RO2 Ex) were therefore studied early after liver transplantation. METHODS Ten patients with an intra- and post-operative vasopressor-dependent systemic vasodilation were studied early after liver transplantation during sedation and mechanical ventilation. To achieve target MAP levels of 60, 75 and 90 mm Hg, the norepinephrine infusion rate was randomly and sequentially titrated. At each target MAP, data on cardiac index (CI), RBF and GFR were obtained by transpulmonary thermodilution (PiCCO), the renal vein thermodilution technique and renal extraction of chromium ethylenediaminetetraaceticacid (51 Cr-EDTA), respectively. Renal oxygen consumption (RVO2 ) and extraction (RO2 Ex) were calculated according to standard formulas. RESULTS At a target MAP of 75 mm Hg, CI (13%), RBF (18%), RDO2 (24%), GFR (31%) and RVO2 (20%) were higher while RO2 Ex was unchanged compared to a target MAP of 60 mm Hg. Increasing MAP from 75 up to 90 mm Hg increased RVR by 38% but had no further effects on CI, RBF, RDO2 or GFR. CONCLUSIONS In patients undergoing liver transplantation, RBF and GFR are pressure-dependent at MAP levels below 75 mm Hg. Our results suggest that MAP should probably be targeted to approximately 75 mm Hg for optimal perioperative renal filtration, perfusion and oxygenation in patients undergoing liver transplantation.
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Forced fluid removal in intensive care patients with acute kidney injury: The randomised FFAKI feasibility trial.
Berthelsen, RE, Perner, A, Jensen, AK, Rasmussen, BS, Jensen, JU, Wiis, J, Behzadi, MT, Bestle, MH
Acta anaesthesiologica Scandinavica. 2018;(7):936-944
Abstract
BACKGROUND Accumulation of fluids is frequent in intensive care unit (ICU) patients with acute kidney injury and may be associated with increased mortality and decreased renal recovery. We present the results of a pilot trial assessing the feasibility of forced fluid removal in ICU patients with acute kidney injury and fluid accumulation of more than 10% ideal bodyweight. METHODS The FFAKI-trial was a pilot trial of forced fluid removal vs standard care in adult ICU patients with moderate to high risk acute kidney injury and 10% fluid accumulation. Fluid removal was done with furosemide and/or continuous renal replacement therapy aiming at net negative fluid balance > 1 mL/kg ideal body weight/hour until cumulative fluid balance calculated from ICU admission reached less than 1000 mL. RESULTS After 20 months, we stopped the trial prematurely due to a low inclusion rate with 23 (2%) included patients out of the 1144 screened. Despite the reduced sample size, we observed a marked reduction in cumulative fluid balance 5 days after randomisation (mean difference -5814 mL, 95% CI -2063 to -9565, P = .003) with forced fluid removal compared to standard care. While the trial was underpowered for clinical endpoints, no point estimates suggested harm from forced fluid removal. CONCLUSIONS Forced fluid removal aiming at 1 mL/kg ideal body weight/hour may be an effective treatment of fluid accumulation in ICU patients with acute kidney injury. A definitive trial using our inclusion criteria seems less feasible based on our inclusion rate of only 2%.
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Renal stress and kidney injury biomarkers in response to endurance cycling in the heat with and without ibuprofen.
McDermott, BP, Smith, CR, Butts, CL, Caldwell, AR, Lee, EC, Vingren, JL, Munoz, CX, Kunces, LJ, Williamson, K, Ganio, MS, et al
Journal of science and medicine in sport. 2018;(12):1180-1184
Abstract
UNLABELLED Exercise, especially in the heat, can contribute to acute kidney injury, which can expedite chronic kidney disease onset. The additional stress of ibuprofen use is hypothesized to increase renal stress. OBJECTIVES To observe the effects of endurance cycling in the heat on renal function. Secondarily, we investigated the effect of ibuprofen ingestion on kidney stress. DESIGN Randomized, placebo controlled and observational methods were utilized. METHODS Forty cyclists (52±9y, 21.7±6.5% body fat) volunteered and completed an endurance cycling event (5.7±1.2h) in the heat (33.2±5.0°C, 38.4±10.7% RH). Thirty-five participants were randomized to ingest a placebo (n=17) or 600mg ibuprofen (n=18) pre-event. A blood sample was drawn before and following the event. Serum creatinine was assessed by colorimetric assay. An ELISA was used to measure serum neutrophil gelatinase-associated lipocalin. Fractional excretion of sodium was calculated after urinary and serum electrolyte analyses. RESULTS Placebo versus ibuprofen groups contributed no significant difference in any variable (p>0.05). Serum creatinine significantly increased from pre- (0.52±0.14mg/dL) to post-event (0.88±0.21mg/dL; p<0.001). Serum neutrophil gelatinase-associated lipocalin significantly increased (pre: 68.51±17.54ng/mL; post: 139.12±36.52ng/mL; p<0.001) and fractional excretion of sodium was significantly reduced from pre- (0.52±0.24%) to post-event (0.27±0.18%; p<0.001). CONCLUSIONS Changes in renal biomarkers suggest mild acute kidney injury and reduced kidney function during a single bout of endurance cycling in the heat, without influence from moderate ibuprofen ingestion.
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[Effect of the ischemic post-conditioning on the prevention of the cardio-renal damage in patients with acute ST-segment elevation myocardial infarction after primary percutaneous coronary intervention].
Wang, YY, Li, T, Liu, YW, Liu, BJ, Hu, XM, Wang, Y, Gao, WQ, Wu, P, Huang, L, Li, X, et al
Zhonghua xin xue guan bing za zhi. 2017;(4):277-282
Abstract
Objective: To evaluate the effect of the ischemic post-conditioning (IPC) on the prevention of the cardio-renal damage in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI). Methods: A total of 251 consecutive STEMI patients underwent PPCI in the heart center of Tianjin Third Central Hospital from January 2012 to June 2014 were enrolled in this prospective, randomized, control, single-blinded, clinical registry study. Patients were randomly divided into IPC group (123 cases) and control group (128 cases) with random number table. Patients in IPC group underwent three times of inflation/deflation with low inflation pressure using a balloon catheter within one minute after culprit vessel blood recovery, and then treated by PPCI. Patients in control group received PPCI procedure directly. The basic clinical characteristics, incidence of reperfusion arrhythmia during the procedure, the rate of electrocardiogram ST-segment decline, peak value of myocardial necrosis markers, incidence of contrast induced acute kidney injury(CI-AKI), and one-year major adverse cardiovascular events(MACE) which including myocardial infarction again, malignant arrhythmia, rehospitalization for heart failure, repeat revascularization, stroke, and death after the procedure were analyzed between the two groups. Results: The age of IPC group and control group were comparable((61.2±12.6) vs. (64.2±12.1) years old, P=0.768). The incidence of reperfusion arrhythmia during the procedure was significantly lower in the IPC group than in the control group(42.28% (52/123) vs. 57.03% (73/128), P=0.023). The rate of electrocardiogram ST-segment decline immediately after the procedure was significantly higher in the IPC group than in the control group (77.24% (95/123) vs. 64.84% (83/128), P=0.037). The peak value of myocardial necrosis markers after the procedure were significantly lower in the IPC group than in the control group(creatine kinase: 1 257 (682, 2 202) U/L vs. 1 737(794, 2 816)U/L, P=0.029; creatine kinase-MB: 123(75, 218)U/L vs.165(95, 288)U/L, P=0.010). The rate of CI-AKI after the procedure was significantly lower in the IPC group than in the control group(5.69%(7/123) vs. 14.06%(18/128), P=0.034). The rate of the one-year MACE was significantly lower in the IPC group than in the control group(7.32%(9/123) vs. 15.63% (20/128), P=0.040). Conclusion: The IPC strategy performed eight before PPCI can reduce myocardial ischemia- reperfusion injury, decline the rates of CI-AKI and one-year MACE significantly in STEMI patients, thus has a significant protective effect on heart and kidney in STEMI patients. Clinical Trial Registration Chinese Clinical Trials Registry, ChiCTR-ICR-15006590.
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Thiamine as a Renal Protective Agent in Septic Shock. A Secondary Analysis of a Randomized, Double-Blind, Placebo-controlled Trial.
Moskowitz, A, Andersen, LW, Cocchi, MN, Karlsson, M, Patel, PV, Donnino, MW
Annals of the American Thoracic Society. 2017;(5):737-741
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RATIONALE Acute kidney injury (AKI) is common in patients with sepsis and has been associated with high mortality rates. The provision of thiamine to patients with sepsis may reduce the incidence and severity of sepsis-related AKI and thereby prevent renal failure requiring renal replacement therapy (RRT). OBJECTIVES To test the hypothesis that thiamine supplementation mitigates kidney injury in septic shock. METHODS This was a secondary analysis of a single-center, randomized, double-blind trial comparing thiamine to placebo in patients with septic shock. Renal function, need for RRT, timing of hemodialysis catheter placement, and timing of RRT initiation were abstracted. The baseline creatinine and worst creatinine values between 3 and 24 hours, 24 and 48 hours, and 48 and 72 hours were likewise abstracted. RESULTS There were 70 patients eligible for analysis after excluding 10 patients in whom hemodialysis was initiated before study drug administration. Baseline serum creatinine in the thiamine group was 1.2 mg/dl (interquartile range, 0.8-2.5) as compared with 1.8 mg/dl (interquartile range, 1.3-2.7) in the placebo group (P = 0.3). After initiation of the study drug, more patients in the placebo group than in the thiamine group were started on RRT (eight [21%] vs. one [3%]; P = 0.04). In the repeated measures analysis adjusting for the baseline creatinine level, the worst creatinine levels were higher in the placebo group than in the thiamine group (P = 0.05). CONCLUSIONS In this post hoc analysis of a randomized controlled trial, patients with septic shock randomized to receive thiamine had lower serum creatinine levels and a lower rate of progression to RRT than patients randomized to placebo. These findings should be considered hypothesis generating and can be used as a foundation for further, prospective investigation in this area.
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Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial.
Doig, GS, Simpson, F, Bellomo, R, Heighes, PT, Sweetman, EA, Chesher, D, Pollock, C, Davies, A, Botha, J, Harrigan, P, et al
Intensive care medicine. 2015;(7):1197-208
Abstract
IMPORTANCE Acute kidney injury (AKI) is characterized by severe loss of glomerular filtration rate (GFR) and is associated with a prolonged intensive care unit (ICU) stay and increased risk of death. No interventions have yet been shown to prevent AKI or preserve GFR in critically ill patients. Evidence from mammalian physiology and small clinical trials suggests higher amino acid intake may protect the kidney from ischemic insults and thus may preserve GFR during critical illness. OBJECTIVE To determine whether amino acid therapy, achieved through daily intravenous (IV) supplementation with standard amino acids, preserves kidney function in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS Multicenter, phase II, randomized clinical trial conducted between December 2010 and February 2013 in the ICUs of 16 community and tertiary hospitals in Australia and New Zealand. Participants were adult critically ill patients expected to remain in the study ICU for longer than 2 days. INTERVENTIONS Random allocation to receive a daily supplement of up to 100 g of IV amino acids or standard care. MAIN OUTCOMES AND MEASURES Duration of renal dysfunction (primary outcome); estimated GFR (eGFR) derived from creatinine; eGFR derived from cystatin C; urinary output; renal replacement therapy (RRT) use; fluid balance and other measures of renal function. RESULTS 474 patients were enrolled and randomized (235 to standard care, 239 to IV amino acid therapy). At time of enrollment, patients allocated to receive amino acid therapy had higher APACHE II scores (20.2 ± 6.8 vs. 21.7 ± 7.6, P = 0.02) and more patients had pre-existing renal dysfunction (29/235 vs. 44/239, P = 0.07). Duration of renal dysfunction after enrollment did not differ between groups (mean difference 0.21 AKI days per 10 patient ICU days, 95 % CI -0.27 to 1.04, P = 0.45). Amino acid therapy significantly improved eGFR (treatment group × time interaction, P = 0.004), with an early peak difference of 7.7 mL/min/1.73 m(2) (95 % CI 1.0-14.5 mL/min/1.73 m(2), P = 0.02) on study day 4. Daily urine output was also significantly increased (+300 mL/day, 95 % CI 145-455 mL, P = 0.0002). There was a trend towards increased RRT use in patients receiving amino acid therapy (13/235 vs. 25/239, P = 0.062); however, this trend was not present after controlling for baseline imbalance (P = 0.21). CONCLUSION AND RELEVANCE Treatment with a daily IV supplement of standard amino acids did not alter our primary outcome, duration of renal dysfunction. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12609001015235.
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Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled trial.
Stucker, F, Ponte, B, Tataw, J, Martin, PY, Wozniak, H, Pugin, J, Saudan, P
Critical care (London, England). 2015;(1):91
Abstract
INTRODUCTION A systemic anticoagulation is often required to prevent circuit and filter clotting in ICU patients undergoing continuous renal replacement therapy (CRRT). A regional citrate-based anticoagulation (RCA) does not induce a systemic anticoagulation and prolongs the filter lifespan, but metabolic side-effects have been associated with this therapy. We conducted a randomized controlled trial with patients requiring CRRT to determine whether RCA using a balanced predilution replacement fluid is more effective than heparin in terms of renal replacement delivered dose and safety profile. METHODS One hundred and three patients with AKI requiring CRRT were included. The patients were randomized to either CRRT with RCA or heparin anticoagulation. Primary endpoints were effective daily delivered RRT dose during the first 3 days of CRRT and filter lifespan. Secondary endpoints were 28-day and 90-day survival and severe metabolic complications and bleeding disorders. RESULTS Median CRRT duration was 3.0 (2-6) days. Effective delivered daily RRT doses were 29 ± 3 and 27 ± 5 mL/kg/hr in the RCA and heparin groups, respectively (p = 0.005). Filter lifespans were 49 ± 29 versus 28 ± 23 hrs in the RCA and heparin groups (p = 0.004). Survival rates at 28 and 90 days were 80-74% in the RCA and 74-73% in the heparin group. Electrolytes and acid-base disturbances were uncommon and transient in patients treated with RCA. CONCLUSIONS These results show that RCA is superior to heparin-based anticoagulation in terms of delivered RRT dose and filter life span and is a safe and feasible method. This does not translate into an improvement in short term survival. TRIAL REGISTRATION ClinicalTrials.gov NCT01269112 . Registered 3rd January 2011.